A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHF) associated with approved multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized trials comparing arms with and without an FDA-approved VEGFR TKI. Statistical analyses calculated the relative risk (RR) and 95% confidence intervals (CI). A total of 10,647 patients from 16 phase III trials and 5 phase II trials were selected. All grade CHF occurred in 138 of 5752 (2.39%) patients receiving VEGFR TKIs and 37 of 4895 (0.75%) patients in the non-TKI group. High-grade CHF occurred in 17 of 1426 (1.19%) patients receiving VEGFR TKIs and 8 of 1232 (0.65%) patients in the non-TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was 2.69 (. p<. 0.001; 95% CI: 1.86 to 3.87) and 1.65 (. p=. 0.227, 95% CI: 0.73 to 3.70), respectively. The RR of relatively specific TKIs (axitinib) was similar to relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib).
